Bitarafan Sara, Pybus Alyssa F, Rivera Moctezuma Felix G, Adibi Mohammad, Franklin Tina C, Singer Annabelle C, Wood Levi B
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia, USA.
APL Bioeng. 2025 Jul 8;9(3):036102. doi: 10.1063/5.0261497. eCollection 2025 Sep.
Current clinical trials are investigating gamma frequency sensory stimulation as a potential therapeutic strategy for Alzheimer's disease (AD); yet, we lack a comprehensive picture of the effects of this stimulation on multiple aspects of brain function. We previously showed that exposing mice to visual flickering stimulation increased mitogen activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cells signaling in the visual cortex (VC) in a manner dependent on the duration and frequency of stimulation. Because these pathways control multiple neuronal and glial functions, here we aimed to define the transcriptional effects of different frequencies and durations of audiovisual flicker (AV flicker) stimulation on multiple brain functions. Within the VC, we found that all stimulation frequencies caused fast activation of a module of immune genes within 0.5 h and slower suppression of synaptic genes after 4 h. In the hippocampus, we found that a 20 Hz AV flicker activated a module of genes associated with mitochondrial function, metabolism, and synaptic translation, while 10 Hz rapidly suppressed a module of genes linked to neurotransmitter activity. Collectively, our data indicate that the frequency and duration of AV flicker stimulation control immune, neuronal, and metabolic genes in multiple regions of the brain affected by AD.
目前的临床试验正在研究γ频率感觉刺激作为治疗阿尔茨海默病（AD）的一种潜在策略；然而，我们尚缺乏关于这种刺激对脑功能多个方面影响的全面认识。我们之前发现，让小鼠暴露于视觉闪烁刺激下，可增加丝裂原活化蛋白激酶和活化B细胞核因子κB信号通路在视觉皮层（VC）中的活性，其方式取决于刺激的持续时间和频率。由于这些信号通路控制多种神经元和神经胶质细胞功能，因此我们旨在确定不同频率和持续时间的视听闪烁（AV闪烁）刺激对多种脑功能的转录影响。在VC内，我们发现所有刺激频率在0.5小时内均可快速激活一个免疫基因模块，而在4小时后则会较慢地抑制突触基因。在海马体中，我们发现20赫兹的AV闪烁可激活一个与线粒体功能、代谢和突触翻译相关的基因模块，而10赫兹则会迅速抑制一个与神经递质活性相关的基因模块。总体而言，我们的数据表明，AV闪烁刺激的频率和持续时间可控制受AD影响的大脑多个区域中的免疫、神经元和代谢基因。
